This application is in the general area of polymeric coating materials which can be applied to surfaces of substrates used in analytical and sensing devices to promote specific recognition of the target analyte while minimizing non-specific adsorption of other molecules in the sampling solution.
There is a need to improve the selectivity and sensitivity of bioaffinity and diagnostic sensors, especially for use in screening assays and libraries for DNA/RNA and proteins. A common approach to diagnostic sensor design involves the measurement of the specific binding of a particular component of a physiological sample. Typically, physiological samples of interest (e.g. blood samples) are complex mixtures of many components that all interact to varying degrees with surfaces of diagnostic sensors. However, the aim of a diagnostic sensor is to probe only the specific interaction of one component while minimizing all other unrelated interactions. In the case of sensors in contact with blood, proteins, glycoproteins and/or saccharides, as well as cells, often adsorb non-specifically onto the sensor surface. This impairs both selectivity and sensitivity, two highly important performance criteria in bioaffinity sensors.
A variety of materials and surfaces is used in analytical and sensor devices, such as glass, silicon wafers, metals or metallized surfaces and metal oxides as bulk or coating materials. The choice of the materials is closely related to the particular sensing technique used. If surface plasmon resonance is used as an analytical or sensing method, the chips will consist of a substrate coated with a metal such as gold. In the case of analytical or sensor chips to be used in combination with specific optical detection sensor chips to be used in combination with specific optical detection techniques, such as fluorescence spectroscopy, optical waveguide techniques or a combination of the two, optically transparent substrates and/or coatings are often needed. Metal oxides or metal oxide coatings are particularly suitable in such cases, in view of their stability, inertness and optical transparency. Polymeric materials are traditionally used for applications in lateral flow assays or multiwell plate assays. Glass or silicon based materials are often used for capillary electrophoresis applications. Both polymeric and glass type materials are used in fiberoptics.
Independent of the analytical or sensing technique used, there is a basic need for surface modification of the chips, as these materials and surfaces do not have the necessary properties in terms of controlled adsorption phenomena in a given detection or sensing application. There is a need for simple, cost-effective treatment materials and methods that effectively reduce non-specific interactions at or adsorption onto metal oxide-based sensor surfaces while introducing a specific binding interaction with the target analyte. Such specific recognition, binding and detection are often achieved through key-lock type of chemical or biological interactions such as antibody-antigen interactions.
The application of multifunctional polymers in implants can be employed to control biological interactions that determine a bioresponse to an implant. Here the same principles of recognition, specificity and suppression of nonspecific adsorption are relevant. An example is the selection of attaching cells in a biological response, where suppression of nonspecific adsorption of proteins from the body fluids can suppress the nonspecific attachment of cells and the inclusion of biospecific recognition ligands, such as adhesion peptides, can enhance the attachment of a specific cell population or subpopulation.
The use of functional polymers and copolymers is an approach often chosen in the biomaterial area to modify surface properties or cell-to-cell interactions. For example, U.S. Pat. Nos. 5,573,934 and 5,626,863 to Hubbell et al. disclose hydrogel materials containing a water-soluble region such as polyethylene glycol and a biodegradable region, including various biodegradable polymers such as polylactide and polyglycolide, terminated with photopolymerizable groups such as acrylates. These materials can be applied to a tissue surface and polymerized, for example, to form tissue coatings. These materials are adhered to tissue surfaces by polymerizing the photopolymerizable groups on the materials after they have been applied to the tissue surface. U.S. Pat. Nos. 5,462,990 and 5,627,233 to Hubbell et al. disclose multifunctional polymeric materials for use in inhibiting adhesion and immune recognition between cells and tissues. The materials include a tissue-binding component (polycation) and a tissue non-binding component (polyanion). In particular, Hubbell discloses various PEG/PLL copolymers, with molecular weights greater than 300, with structures that include AB copolymers, ABA copolymers, and brush-type copolymers. These polymers are being commercially developed for use as tissue sealants and to prevent surgical adhesions. WO 98/47948 ‘Multifunctional Polymeric Tissue Coatings’ by Hubbell et al. describes another class of polymer, grafted polyionic copolymers that are able to attach to biological and non-biological samples in order to control cell-surface and cell-cell and tissue-surface interactions in biomedical applications. These materials have not been used to coat devices or devices for implantation, however, especially devices having metal oxide or other surfaces which may not adhere well to receptors or other ligands used for sensing or analysis.
It is therefore an object of the present invention to provide materials which can be used to control and modify cell-surface and cell-cell interactions, especially on the surface of devices and implants.
It is a further object of the present invention to provide methods for application of these materials to a substrate which is rapid, inexpensive, and flexible.
It is another object of the present invention to provide a stable polymeric material that can be applied simply, quickly and cost-effectively to charged surfaces of analytical devices and sensor chips for applications where it is essential to establish a specific binding interaction while preventing the unwanted non-specific interactions that typically occur at surfaces in contact with physiological and other types of samples. analytical or diagnostic devices, culture surfaces, sensor chips, and implants.